Ab-initio Quantum Mechanical Calculations of NMR Chemical Shifts in Nucleic Acids Constituents III Chemical Shift Variations due to Base Stacking

Abstract

Ab inito computations of the different contributions to chemical shift variations due to intra and interstrand stacking are reported for the GC, CG, AT and TA sequences of a B DNA helix. The results obtained for the non hydrogen atoms of the GC stacks show that the chemical shift variations are mainly due to the polarization contribution, the term which decreases slowly with the intermolecular distance. Because of the weaker polarity of adenine and thymine the geometric and polarization contributions are of closer absolute magnitude for the non hydrogen atoms of the intrastrand stacks but the polarization term is the determining contribution in the corresponding interstrand stacks. For the protons which undergo smaller shifts due to the polarization (or electric field effects) the role of the geometric contribution is more important and is even the leading one for the hydrogens of cytosine and thymine in the case of intrastrand stacking. The charge transfer plus exchange term has a non negligeable value for a limited number of cases corresponding to the shortest intermolecular interatomic distances. These results are discussed in relation with the qualitative differences observed between the proton and carbon spectra of dinucleotides and B-DNA duplexes.

Quantum mechanical calculations of NMR chemical shifts in nucleic acids

“…The increased shielding measured for nuclei located above the plane of the nucleic acid bases is identical for any kind of nucleus having the same position in space. However, this term has a larger relative importance, when compared to the total variation of shielding due to a change of molecular conformation or environment, for protons than for other nuclei such as 13 C, 15 N or 31 P (Ferchiou & Giessner-Prettre, 1985;Giessner-Prettre, 1986 and unpublished results) since the chemical shift variations measured for protons can, in the case of base stacking for example (Cheng et al 1980), be accounted for by this single term. Therefore the variation of the magnetic anisotropy shielding with the nature of the base and/or its tautomeric form will be discussed in the part of this review concerned with protons.…”

“…The first, put into evidence by non-empirical calculations of AS E (Day & Buckingham, 1976;Ferchiou & Giessner-Prettre, unpublished results) is the use of the same value of A and B for the different type of XH bonds which are present in nucleic acids and of a single value of B for all directions of E. The second is due to the approximations used to calculate the molecular wavefunction on one hand, and the electric field due to this wavefunction on the other (Ferchiou & Giessner-Prettre, unpublished results). However the polarization contribution to chemical shift values should not be systematically overlooked (Giessner-Prettre et al 1981;Kan et al 1982) for at least two reasons; one is the occurrence of situations where it is the leading contribution (Giessner-Prettre, 1984, 1986 and the other is that it is the long range contribution (Giessner-Prettre & Ferchiou, 1983), a feature which can be important in the case of polymers carrying formal charges such as nucleic acids.…”

“…On the contrary 13 C-NMR spectroscopy of nuclei acids has been developing more slowly, although the number of such studies on oligonucleotides and short helices has begun to increase in the last two or three years (Lankhorst et al 1983;Alderfer et al 1984;Box et al 1984;Borer et al 1984;Stone et al 1985Stone et al , 1986, while good quality spectra have been measured for nucleosides (Jones et al 1970), nucleotides (Dorman & Roberts, 1970) and even a polynucleotide (Mantsch & Smith, 1972) some fifteen years ago. Since theoretical calculations of carbon shifts have begun to be approached only recently (Giessner-Prettre, 1984,1986 the large difference between the development of *H-and 31 P-NMR on one hand and 13 C spectroscopy on the other suggests the importance of quantum mechanical calculations for the interpretation of experimental NMR chemical shifts of molecules such as the nucleic acids for which the measured data depend not only on the structure of the compound studied but also to a large extent on the conditions of the experiment.…”

Accurate ab initio prediction of NMR chemical shifts of nucleic acids and nucleic acids/protein complexes

“…On the one hand, NMR structure determination of these molecules suffers from the scarcity of accessible nuclear Overhauser effect (NOE) derived distance constraints and the complicated interpretation of these few constraints caused by the high degree of flexibility especially in RNA ( 34 ). On the other hand, quantum chemical calculations on small test systems like mono-nucleotides, tri-nucleotides or base pairs showed that sugar ring puckering ( 35 – 39 ), exocyclic and glycosidic torsions ( 37 , 38 , 40 ), hydrogen bonds between base pairs ( 41 – 43 ) and ring current effects brought about by base stacking ( 44 – 47 ) have a profound influence on the chemical shifts. These can be used to predict structural features ( 46 – 51 ).…”

Random coil carbon chemical shifts of deoxyribonucleic acids

“…Not much work has been done on carbon chemical shifts of random coil DNA sequences [5], although carbon chemical shifts have a wider chemical shift spread than proton and contain wealthy structure information on nucleic acids [6][7][8]. DNA base carbon resonance frequencies have been shown to be sensitive to hydrogen bonding, base stacking, sugar conformation, and the glycosidic torsion angle by ab initio quantum mechanical calculations [9,10] and experimental NMR studies [11][12][13][14], making carbon chemical shifts useful for monitoring DNA-drug binding [15] and DNA-protein binding [16].…”